Schulze, Marco H.

[["dc.bibliographiccitation.firstpage","157"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Breast Cancer Research and Treatment"],["dc.bibliographiccitation.lastpage","166"],["dc.bibliographiccitation.volume","87"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Simon, Alfred"],["dc.contributor.author","Binder, L."],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Emons, G."],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Einspanier, Almuth"],["dc.date.accessioned","2018-11-07T10:45:48Z"],["dc.date.available","2018-11-07T10:45:48Z"],["dc.date.issued","2004"],["dc.description.abstract","Relaxin (RLX) is known to induce remodeling of benign stromal tissues through upregulation of matrix metalloproteases (MMPs). Recently, we could show that RLX also induces MMPs in breast cancer cells and enhances in vitro invasiveness. To investigate its potential role for progression of breast cancer in vivo, RLX serum concentrations were determined in 160 breast cancer patients during post-surgical follow-up. RLX concentrations in cancer patients were significantly higher than in a control population of healthy blood donors and patients with various other diseases (0.47 versus 0.29 ng/ml, p < 0.0001). There was a significant difference between patients with metastases (0.62 ng/ml) and those without (0.38 ng/ml, p < 0.0001). Overall survival was shorter in RLX-positive (>0.4 ng/ml) than in RLX-negative patients (p = 0.016). Cox regression analysis showed that RLX was not an independent variable, in contrast to metastatic disease and primary lymph node involvement. Taken together, the detection of elevated RLX concentrations especially in patients with metastases supports the assumption that there is a role for RLX in tissue remodeling during breast cancer progression."],["dc.identifier.doi","10.1023/B:BREA.0000041622.30169.16"],["dc.identifier.isi","000223914900005"],["dc.identifier.pmid","15377840"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47592"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Kluwer Academic Publ"],["dc.relation.issn","0167-6806"],["dc.title","Elevated concentrations of serum relaxin are associated with metastatic disease in breast cancer patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","789"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","MHR Basic science of reproductive medicine"],["dc.bibliographiccitation.lastpage","796"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Husen, B."],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Einspanier, Almuth"],["dc.date.accessioned","2018-11-07T10:07:56Z"],["dc.date.available","2018-11-07T10:07:56Z"],["dc.date.issued","2002"],["dc.description.abstract","Until recently, relaxin (RLX) has been known predominantly for its effects on the reproductive system, where it induces remodelling of the extracellular matrix and up-regulation of matrix metalloproteases (MMPs). In solid cancers, tissue remodelling and MNIP activation are essential for invasion and metastasis. We therefore investigated the effect of RLX on invasiveness and MNIP expression of human breast cancer cell lines. Upon incubation with porcine RLX, the invasiveness of SK-BR3 cells was significantly increased. Similar effects could be achieved in MCF-7 cells, especially when RLX was combined with epidermal growth factor. Enhanced invasiveness was accompanied by up-regulation of NIMP production and could be almost completely blocked by the NIMP inhibitor FN 439. Zymography revealed increased secretion of MMP-2, -7 and -9, associated with upregulated mRNA concentrations of MMP-2, -9, -13 and -14. mRNA expression levels of MMP-1, -3, -7, -8, -10, -11, -12 and of tissue inhibitors of metalloproteases-1, -2, -3 and -4 were either very low or not detectably influenced by RLX. Taken together, RLX enhances in-vitro invasiveness of breast cancer cell lines by induction of MMP expression. It remains to be clarified whether RLX might play a similar role in vivo and promote tumour progression."],["dc.identifier.doi","10.1093/molehr/8.9.789"],["dc.identifier.isi","000177970900001"],["dc.identifier.pmid","12200455"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39378"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1360-9947"],["dc.title","Relaxin enhances in-vitro invasiveness of breast cancer cell lines by up-regulation of matrix metalloproteases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1543"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Carcinogenesis"],["dc.bibliographiccitation.lastpage","1549"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Robinson, S. C."],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Balkwill, F. R."],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2018-11-07T10:46:34Z"],["dc.date.available","2018-11-07T10:46:34Z"],["dc.date.issued","2004"],["dc.description.abstract","Apart from the neoplastic cells, malignant tumours consist of the extracellular matrix (ECM) and normal cells, in particular tumour-associated macrophages (TAM). To understand the mechanisms by which TAM can influence tumour cell invasion we co-cultured the human breast cancer cell lines MCF-7, SK-BR-3 and the benign mammary epithelial cell line hTERT-HME1 with macrophages. Co-incubation enhanced invasiveness of the tumour cells, while hTERT-HME1 remained non-invasive. Addition of the broad-spectrum matrix metalloprotease (MMP)-inhibitor FN 439, neutralizing MMP-9 or tumour necrosis factor-alpha (TNF-alpha) antibodies reduced invasiveness to basal levels. As shown by zymography, all cell lines produced low amounts of MMP-2, -3, -7 and -9 under control conditions. Basal MMP production by macrophages was significantly higher. Upon co-incubation, supernatant levels of MMPs -2, -3, -7 and -9 increased significantly, paralleled by an increase of MMP-2 activation. MMP-2 and -9 induction could be blocked by TNF-alpha antibodies. Co-culture of macrophages and hTERT-HME1 did not lead to MMP induction. In the co-cultures, mRNAs for MMPs and TNF-alpha were significantly up-regulated in macrophages, while the mRNA concentrations in the tumour cells remained unchanged. In summary, we have found that co-cultivation of tumour cells with macrophages leads to enhanced invasiveness of the malignant cells due to TNF-alpha dependent MMP induction in the macrophages."],["dc.identifier.doi","10.1093/carcin/bgh146"],["dc.identifier.isi","000223142700027"],["dc.identifier.pmid","15044327"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47775"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0143-3334"],["dc.title","Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-alpha dependent up-regulation of matrix metalloproteases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5454"],["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"],["dc.bibliographiccitation.lastpage","5459"],["dc.bibliographiccitation.volume","103"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Hagemann, T."],["dc.contributor.author","Gradl, D."],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Siemes, S."],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2018-11-07T09:59:40Z"],["dc.date.available","2018-11-07T09:59:40Z"],["dc.date.issued","2006"],["dc.description.abstract","Interactions between neoplastic and stromal cells contribute to tumor progression. Wnt genes, involved in cell migration and often deregulated in cancers, are attractive candidates to regulate these effects. We have recently shown that coculture of breast cancer cells with macrophages enhances invasiveness via matrix metal loproteases and TNF-alpha. Here we demonstrate that coculture of MCF-7 cells and macrophages leads to up-regulation of Writ 5a in the latter. This was accompanied by activation of AP-1/c-Jun in MCF-7. Recombinant Writ 5a mimicked the coculture effect. Writ 5a was also detectable in tumor-associated macrophages in primary breast cancers. Experiments with agonists and antagonists of Writ signaling revealed that a functional canonical pathway in the tumor cells was a necessary prerequisite; however, noncanonical signaling via Writ 5a and the Jun-N-terminal kinase pathway was critical for invasiveness. It was also responsible for induction of matrix metalloprotease-7, known to release TNF-alpha. All these effects could be antagonized by dickkopf-1. Our results indicate that Wnt 5a is essential for macrophage-induced invasiveness, because it regulates tumor cell migration as well as proteolytic activity of the macrophages. The function of Writ 5a as either a suppressor or promoter of malignant progression seems to be modulated by intercellular interactions. Writ 5a detection in tumor-associated macrophages in breast cancer biopsies supports the assumption that similar events play a role in vivo."],["dc.description.sponsorship","Medical Research Council [G0601867]"],["dc.identifier.doi","10.1073/pnas.0509703103"],["dc.identifier.isi","236636400040"],["dc.identifier.pmid","16569699"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37646"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Chuang, H.-N."],["dc.contributor.author","vanRossum, D. V."],["dc.contributor.author","Sieger, Dirk"],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Bayerlova, M."],["dc.contributor.author","Wenske, Britta"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Schulz, M."],["dc.contributor.author","Dehghani, Faramarz"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Hanisch, U.-K."],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T09:23:22Z"],["dc.date.available","2018-11-07T09:23:22Z"],["dc.date.issued","2013"],["dc.format.extent","S216"],["dc.identifier.isi","000320408400701"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29559"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.eventlocation","Berlin, GERMANY"],["dc.relation.issn","0894-1491"],["dc.title","CARCINOMA CELLS MISUSE THE HOST TISSUE DANGER RESPONSE TO INVADE THE BRAIN"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]